British Journal of Ophthalmology, 1979, 63, 325-330
Mechanisms in ocular hypertension R. MAPSTONE From St. Paul's Eye Hospital, Liverpool
SUMMARY This paper investigates the hypothesis that intermittent partial angle closure is one of the causes of ocular hypertension. 139 eyes from 76 patients with ocular hypertension were provoked with pilocarpine and phenylephrine. Four distinct responses appeared. Firstly, in 39 eyes (from 24 patients, 32%) gonioscopic closure of part or all of the angle appeared. Secondly, in 30 eyes (from 19 patients, 25 %) no angle closure occurred but there was a substantial pigment release into the aqueous. Thirdly, in 9 eyes (from 8 patients, 11 %) both angle closure and pigment release occurred. Finally, in 61 eyes (from 36 patients, 59%) neither angle closure nor pigment release appeared. (Since the 2 eyes of a patient did not always behave in the same way, for example, 1 eye might develop angle closure and the other not, 1 patient may appear in 2 groups.) From the first group 1 eye from each patient was randomly chosen for iridectomy. A repeat provocative test at least 1 year later produced a significantly different result. It is considered that the evidence obtained in this study supports the hypothesis that intermittent partial angle closure is one of the causes of ocular hypertension.
There is no reason to suppose that ocular hypertension has one unique cause, and a clinically indistinguishable picture has been shown to occur in some eyes at risk to the development of closedangle glaucoma (Mapstone, 1979a). This paper investigates the hypothesis that one of the causes of ocular hypertension is intermittent partial angle closure. Material and methods
was recorded, tonography was repeated, and another dose of pilocarpine and phenylephrine instilled. Finally, after another 1j hours (that is 21 hours from the start of the test) pressure was recorded and tonography repeated. Gonioscopy was done on every patient at the start and termination of the test. Thirty-three patients developed partial or complete gonioscopic closure of the angle in I or both eyes. One eye from each of these patients was then randomly selected for a peripheral iridectomy. The result of a provocative test before and at least 1 year after iridectomy are recorded (this represents 19 patients; in 14 cases 1 year has not yet elapsed since an iridectomy was
One hundred and thirty-nine eyes from 76 patients were studied. They were selected on the following criteria: (1) No story suggestive of intermittent closed-angle glaucoma; (2) no glaucomatous field done). defect; (3) a gonioscopically open angle with no The critical measurement at the inception of peripheral anterior synechiae; (4) a mean applanation angle closure is the distance between iris and cornea pressure on 3 consecutive occasions of 21 mmHg or just internal to the limbus (Mapstone, 1979b). more; (5) no anterior segment exfoliation; (6) no Angles were therefore divided into 3 groups: (1) Iridovenous occlusive disease; (7) no family history of corneal distance less than one-quarter of corneal glaucoma. thickness; (2) iridocorneal distance about oneThe eyes were provoked as follows: At zero hour quarter of corneal thickness; and (3) iridocorneal intraocular pressure was measured, facility of outflow distance greater than one-quarter of corneal thickrecorded, and pilocarpine drops 2% plus phenyle- ness. The gap was estimated in the temporal phrine drops 10% instilled. Approximately lI hours quadrant. from the start of the test the intraocular pressure During each provocative test attention was also directed to the amount of pigment released into the Address for reprints: Mr R. Mapstone, St. Paul's Eye aqueous and was subjectively classified as follows: (1) Pigment absent; (2) pigment present, but the Hospital, Old Hall Street, Liverpool L3 9PF 325
R.
326
26 24 P 22 20 18
.4 .3
Fig. 1 Response of 139 eyes to provocative testing with pilocarpine (P) and phenylephrine (F). Mean and standard error recorded
C .2 .1
0
1
2
Fig. 2 Response of 39 eyes to provocative testing with pilocarpine (P) and phenylephrine (F). Mean and standard error recorded
Mapstone
3
2
1
0 3 HOURS
.4
26 24 P 22 20 18
.3 C .21
.1 0
1
2
3
0
1
2
3
HO URS number of pigment granules present in a slit beam of 3 mm length could, if necessary, be counted; and (3) pigment present, but to such a degree that a count would be impossible. Results Provocative test result in 139
eyes from
76 patients
Fig. I records the mean response and shows that the first dose of phenylephrine and pilocarpine decreased pressure from a mean of 22-9 to 20-7 mmHg and increased-outflow from a mean of 0-15 to 0-20 [lI/mmHg per min. The second dose increased pressure from a mean of 20 7 to 21-3 mmHg, outflow remained at 0-20. The 4 patterns of outflow response described previously (Mapstone, 1977a, b, 1978) were also shown by this group. However, for the purpose of this paper the responses are analysed as follows. (1) Response of 39 eyes (from 27 patients) that developed gonioscopic angle closure only. Fig. 2 records the result and shows that the first dose of pilocarpine and phenylephrine reduced pressure from a mean of 22-7 to 21-1 mmHg and increased
outflow from a mean of 015 to 019. The second dose increased pressure from a mean of 21 1 to 24-7 mmHg and outflow decreased from a mean of 0 19 to 0-17. The statistics of this group are, however, biased by the fact that 8 eyes from 6 patients developed acute closed-angle glaucoma (gonioscopic closure with an increase in pressure of at least 8 mmHg) during the test. In 8 eyes reductions in pressure and substantial increases in outflow occurred in spite of extensive gonioscopic closure. This fact is obscured by the
analysis. (2) Response of 30 eyes (from 19 patients) that developed no gonioscopic angle closure but released much pigment into the aqueous. Fig. 3 records the result and shows that the first dose of pilocarpine and phenylephrine decreased pressure from a mean of 22 9 to 21-2 mmHg and increased outflow from a mean of 016 to 0-17. The second dose increased pressure from a mean of 21-1 to 21-9 mmHg and outflow decreased from a mean of 0-17 to 0-16. (3) Response of 9 eyes (from 8 patients) that developed both gonioscopic angle closure and much pigment release. Fig. 4 records the result and shows
327
Mechanisms in ocular hypertension
Fig. 3 Response of 30 eyes to
provocative testing with pilocarpine (P) and phenylephrine (F). Mean and standard error recorded
26 24 P 22 20 18
v
,
.4
'iir 3Ic.2 ± 0
I__
.1 0
3
2
1
1
2
3
HOURS
PF
26 24 22 T P 20 18 0
I
p
.4
.3 C .2
Fig. 4 Response of 9 eyes to provocative testing with pilocarpine (P) and phenylephrine (F). Mean and standard error recorded
-,
.1
1
2
3
1
0
3
2
HOURS
Fig. 5 Response of 61 eyes to provocative testing with pilocarpine (P) and phenylephrine (F). Mean and standard error recorded
26 24
1PF W~PFI T
P 22
.4 .3
C.2
i
20 18 0
1
.1 2
3
0
HOURS that the first dose of pilocarpine and phenylephrine decreased pressure from a mean of 21-6 to 20-8 mmHg and increased outflow from a mean of 0-14 to 0-16. The second dose decreased pressure from a mean of 20-8 to 20-2 mmHg and increased outflow from a mean of 0-16 to 0-17. No patient developed acute closed-angle glaucoma. (4) Response of 61 eyes (from 36 patients) that developed neither gonioscopic angle closure nor
1
2
3
pigment release. Fig. 5 records the results and shows that the first dose of pilocarpine and phenylephrine decreased pressure from a mean of 23-3 to 20 mmHg and increased outflow from a mean of 0-15 to 0 22. The second dose decreased pressure from 20 to 19 1 mmHg and increased outflow from 0 22 to 025. An analysis of the overall change in pressure and facility of outflow produced by a provocative test in the different groups is shown in Table 1. It can
R.
328
Mapstone
PF
PF 6 1
24 22
4
T
Fig. 6 Response of 19 eyes to provocative testing with pilocarpine (P) and phenylephrine (F),
3
p
v
C
20 18
.~~~~~~~~ ----i ~ I
before (solid line) and after (interrupted line) a peripheral iridectomy. Mean and standard error recorded
_
2
~~~~~~~
IIF
16 0
1
2
1
0 3 HOURS
Table 1 Significance of the changes in pressure and outflow in various groups of eyes during a provocative test AC
AP t
P
t
P
1-06
NS
1-45
NS
PR only
102
NS
0-36
NS
AC + PR
1-31
NS
1-63
NS
Neither
6 16
Mechanisms in ocular hypertension R. MAPSTONE From St. Paul's Eye Hospital, Liverpool
SUMMARY This paper investigates the hypothesis that intermittent partial angle closure is one of the causes of ocular hypertension. 139 eyes from 76 patients with ocular hypertension were provoked with pilocarpine and phenylephrine. Four distinct responses appeared. Firstly, in 39 eyes (from 24 patients, 32%) gonioscopic closure of part or all of the angle appeared. Secondly, in 30 eyes (from 19 patients, 25 %) no angle closure occurred but there was a substantial pigment release into the aqueous. Thirdly, in 9 eyes (from 8 patients, 11 %) both angle closure and pigment release occurred. Finally, in 61 eyes (from 36 patients, 59%) neither angle closure nor pigment release appeared. (Since the 2 eyes of a patient did not always behave in the same way, for example, 1 eye might develop angle closure and the other not, 1 patient may appear in 2 groups.) From the first group 1 eye from each patient was randomly chosen for iridectomy. A repeat provocative test at least 1 year later produced a significantly different result. It is considered that the evidence obtained in this study supports the hypothesis that intermittent partial angle closure is one of the causes of ocular hypertension.
There is no reason to suppose that ocular hypertension has one unique cause, and a clinically indistinguishable picture has been shown to occur in some eyes at risk to the development of closedangle glaucoma (Mapstone, 1979a). This paper investigates the hypothesis that one of the causes of ocular hypertension is intermittent partial angle closure. Material and methods
was recorded, tonography was repeated, and another dose of pilocarpine and phenylephrine instilled. Finally, after another 1j hours (that is 21 hours from the start of the test) pressure was recorded and tonography repeated. Gonioscopy was done on every patient at the start and termination of the test. Thirty-three patients developed partial or complete gonioscopic closure of the angle in I or both eyes. One eye from each of these patients was then randomly selected for a peripheral iridectomy. The result of a provocative test before and at least 1 year after iridectomy are recorded (this represents 19 patients; in 14 cases 1 year has not yet elapsed since an iridectomy was
One hundred and thirty-nine eyes from 76 patients were studied. They were selected on the following criteria: (1) No story suggestive of intermittent closed-angle glaucoma; (2) no glaucomatous field done). defect; (3) a gonioscopically open angle with no The critical measurement at the inception of peripheral anterior synechiae; (4) a mean applanation angle closure is the distance between iris and cornea pressure on 3 consecutive occasions of 21 mmHg or just internal to the limbus (Mapstone, 1979b). more; (5) no anterior segment exfoliation; (6) no Angles were therefore divided into 3 groups: (1) Iridovenous occlusive disease; (7) no family history of corneal distance less than one-quarter of corneal glaucoma. thickness; (2) iridocorneal distance about oneThe eyes were provoked as follows: At zero hour quarter of corneal thickness; and (3) iridocorneal intraocular pressure was measured, facility of outflow distance greater than one-quarter of corneal thickrecorded, and pilocarpine drops 2% plus phenyle- ness. The gap was estimated in the temporal phrine drops 10% instilled. Approximately lI hours quadrant. from the start of the test the intraocular pressure During each provocative test attention was also directed to the amount of pigment released into the Address for reprints: Mr R. Mapstone, St. Paul's Eye aqueous and was subjectively classified as follows: (1) Pigment absent; (2) pigment present, but the Hospital, Old Hall Street, Liverpool L3 9PF 325
R.
326
26 24 P 22 20 18
.4 .3
Fig. 1 Response of 139 eyes to provocative testing with pilocarpine (P) and phenylephrine (F). Mean and standard error recorded
C .2 .1
0
1
2
Fig. 2 Response of 39 eyes to provocative testing with pilocarpine (P) and phenylephrine (F). Mean and standard error recorded
Mapstone
3
2
1
0 3 HOURS
.4
26 24 P 22 20 18
.3 C .21
.1 0
1
2
3
0
1
2
3
HO URS number of pigment granules present in a slit beam of 3 mm length could, if necessary, be counted; and (3) pigment present, but to such a degree that a count would be impossible. Results Provocative test result in 139
eyes from
76 patients
Fig. I records the mean response and shows that the first dose of phenylephrine and pilocarpine decreased pressure from a mean of 22-9 to 20-7 mmHg and increased-outflow from a mean of 0-15 to 0-20 [lI/mmHg per min. The second dose increased pressure from a mean of 20 7 to 21-3 mmHg, outflow remained at 0-20. The 4 patterns of outflow response described previously (Mapstone, 1977a, b, 1978) were also shown by this group. However, for the purpose of this paper the responses are analysed as follows. (1) Response of 39 eyes (from 27 patients) that developed gonioscopic angle closure only. Fig. 2 records the result and shows that the first dose of pilocarpine and phenylephrine reduced pressure from a mean of 22-7 to 21-1 mmHg and increased
outflow from a mean of 015 to 019. The second dose increased pressure from a mean of 21 1 to 24-7 mmHg and outflow decreased from a mean of 0 19 to 0-17. The statistics of this group are, however, biased by the fact that 8 eyes from 6 patients developed acute closed-angle glaucoma (gonioscopic closure with an increase in pressure of at least 8 mmHg) during the test. In 8 eyes reductions in pressure and substantial increases in outflow occurred in spite of extensive gonioscopic closure. This fact is obscured by the
analysis. (2) Response of 30 eyes (from 19 patients) that developed no gonioscopic angle closure but released much pigment into the aqueous. Fig. 3 records the result and shows that the first dose of pilocarpine and phenylephrine decreased pressure from a mean of 22 9 to 21-2 mmHg and increased outflow from a mean of 016 to 0-17. The second dose increased pressure from a mean of 21-1 to 21-9 mmHg and outflow decreased from a mean of 0-17 to 0-16. (3) Response of 9 eyes (from 8 patients) that developed both gonioscopic angle closure and much pigment release. Fig. 4 records the result and shows
327
Mechanisms in ocular hypertension
Fig. 3 Response of 30 eyes to
provocative testing with pilocarpine (P) and phenylephrine (F). Mean and standard error recorded
26 24 P 22 20 18
v
,
.4
'iir 3Ic.2 ± 0
I__
.1 0
3
2
1
1
2
3
HOURS
PF
26 24 22 T P 20 18 0
I
p
.4
.3 C .2
Fig. 4 Response of 9 eyes to provocative testing with pilocarpine (P) and phenylephrine (F). Mean and standard error recorded
-,
.1
1
2
3
1
0
3
2
HOURS
Fig. 5 Response of 61 eyes to provocative testing with pilocarpine (P) and phenylephrine (F). Mean and standard error recorded
26 24
1PF W~PFI T
P 22
.4 .3
C.2
i
20 18 0
1
.1 2
3
0
HOURS that the first dose of pilocarpine and phenylephrine decreased pressure from a mean of 21-6 to 20-8 mmHg and increased outflow from a mean of 0-14 to 0-16. The second dose decreased pressure from a mean of 20-8 to 20-2 mmHg and increased outflow from a mean of 0-16 to 0-17. No patient developed acute closed-angle glaucoma. (4) Response of 61 eyes (from 36 patients) that developed neither gonioscopic angle closure nor
1
2
3
pigment release. Fig. 5 records the results and shows that the first dose of pilocarpine and phenylephrine decreased pressure from a mean of 23-3 to 20 mmHg and increased outflow from a mean of 0-15 to 0 22. The second dose decreased pressure from 20 to 19 1 mmHg and increased outflow from 0 22 to 025. An analysis of the overall change in pressure and facility of outflow produced by a provocative test in the different groups is shown in Table 1. It can
R.
328
Mapstone
PF
PF 6 1
24 22
4
T
Fig. 6 Response of 19 eyes to provocative testing with pilocarpine (P) and phenylephrine (F),
3
p
v
C
20 18
.~~~~~~~~ ----i ~ I
before (solid line) and after (interrupted line) a peripheral iridectomy. Mean and standard error recorded
_
2
~~~~~~~
IIF
16 0
1
2
1
0 3 HOURS
Table 1 Significance of the changes in pressure and outflow in various groups of eyes during a provocative test AC
AP t
P
t
P
1-06
NS
1-45
NS
PR only
102
NS
0-36
NS
AC + PR
1-31
NS
1-63
NS
Neither
6 16
